Adrenergic control of serotonin release from a midgut carcinoid tumour

A case of recurrent midgut carcinoid tumour with disseminated spread is described, in which the clinical diagnosis was supported by measurements of elevated basal serotonin (5-HT) levels in peripheral blood and increased 5-HT responses to pentagastrin provocation, despite normal urinary levels of 5-hydroxyindoleacetic acid. Preoperative diagnosis was obtained by concomitant determinations of 5-HT in mesenteric and hepatic veins. The carcinoid tumour was studied immunocytochemically using antisera to tyrosine hydroxylase and 5-HT. Neuroendocrine complexes between adrenergic nerve terminals and 5-HT-containing tumour cells could be demonstrated. 5-HT release from tumour cells in suspension was studied in vitro after incubation with adrenoceptor agonists or pentagastrin. Tissue pieces from the tumour were also transplanted into the anterior eye chamber of Sprague-Dawley rats, some of which were subjected to immunosuppression (Cyclosporin A 20 mg/kg s.c.). After 10 days in oculo the tumour transplants (with preserved immunocytochemical characteristics) were stimulated with adrenoceptor agonists. Tumour cells in suspension as well as tumour transplants released 5-HT upon adrenoceptor stimulation but no release was induced by pentagastrin. The pentagastrin test is suggested to cause release of 5-HT in carcinoid tumour patients via release of endogenous catecholamines, in turn activating adrenoreceptors on carcinoid tumour cells.